Ventilator-derived dynamic respiratory system compliance: Comparison with static compliance in children.

Measurement of dynamic lung compliance during breathing requires measurement of esophageal pressure, whereas static respiratory system compliance (Crs) method requires several airway occlusions. Despite their precision these compliance methods are cumbersome and not suitable for evaluation of pulmonary system in intensive care. The current ventilators display dynamic Crs, which, however, is seldom utilized in clinical practice. We studied the feasibility of ventilator-derived dynamic Crs measurement in pulmonary evaluation after congenital cardiac surgery in children. In 50 children static Crs was measured by double-occlusion technique, and compared with simultaneous ventilator-derived dynamic Crs values. The early postoperative dynamic and static Crs showed a correlation (r = 0.57, p < 0.0001), but static Crs was 48% higher than dynamic (p < 0.0001). Dynamic Crs measurement showed no correlation with radiographic lung edema findings, whereas the static Crs showed a negative correlation with radiographic lung edema scoring (r = -0.50, p = 0.0002). Thus ventilator-derived dynamic Crs seems less reliable in postoperative pulmonary evaluation than static Crs.

Assessment of extravascular lung water by ultrasound after congenital cardiac surgery.

BACKGROUND: Lung ultrasounds show vertical artifacts known as B-lines in the presence of increased extravascular lung water (EVLW). We aimed to investigate whether lung ultrasound could estimate EVLW after congenital cardiac surgery. METHODS: This prospective observational study comprised 61 children (age range 3 days to 7.4 years) undergoing congenital cardiac surgery. We compared postoperative B-line scores from lung ultrasounds, early postoperative ultrasound as our primary interest, with corresponding postoperative chest radiography (CXR) lung edema scores, with static lung compliance, and with short-term clinical outcome interpreted as time on mechanical ventilation and length of pediatric intensive care unit (PICU) stay. RESULTS: Our findings showed lung ultrasound B-line scores and CXR lung edema scores as correlating 1-6 hr postoperatively (r2 = 0.41, P < 0.0001), on the first postoperative day (r2 = 0.15, P = 0.004) and on the fourth postoperative day (r2 = 0.28, P = 0.008). The B-line score or CXR lung edema score showed no correlation with lung compliance. We found that in multivariable analyses, with length of perfusion and presence of postoperative complications as covariates, both lung ultrasound (P ≤ 0.02) and CXR (P ≤ 0.002) 1-6 hr postoperatively predicted the length of mechanical ventilation and PICU stay. The interobserver variability was less for lung ultrasound B-line score than for CXR lung edema score (P = 0.001). CONCLUSIONS: Our results show that lung ultrasound in assessment of postoperative EVLW predicted length of mechanical ventilation and stay in the PICU, and it had less interobserver variability than CXR. Accordingly, lung ultrasound may complement CXR in assessment of lung edema after surgery for congenital heart defect. Pediatr Pulmonol. 2017;52:345-352. © 2016 Wiley Periodicals, Inc.

Chronic Hypoxemia in Children With Congenital Heart Defect Impairs Airway Epithelial Sodium Transport.

OBJECTIVE: Ambient hypoxia impairs the airway epithelial Na transport, which is crucial in lung edema reabsorption. Whether chronic systemic hypoxemia affects airway Na transport has remained largely unknown. We have therefore investigated whether chronic systemic hypoxemia in children with congenital heart defect affects airway epithelial Na transport, Na transporter-gene expression, and short-term lung edema accumulation. DESIGN: Prospective, observational study. SETTING: Tertiary care medical center responsible for nationwide pediatric cardiac surgery. PATIENTS: Ninety-nine children with congenital heart defect or acquired heart disease (age range, 6 d to 14.8 yr) were divided into three groups based on their level of preoperative systemic hypoxemia: 1) normoxemic patients (SpO2% ≥ 95%; n = 44), 2) patients with cyanotic congenital heart defect and moderate hypoxemia (SpO2 86-94%; n = 16), and 3) patients with cyanotic congenital heart defect and profound systemic hypoxemia (SpO2 ≤ 85%; n = 39). MEASUREMENTS AND MAIN RESULTS: Nasal transepithelial potential difference served as a surrogate measure for epithelial Na transport of the respiratory tract. Profoundly hypoxemic patients had 29% lower basal nasal transepithelial potential difference (p = 0.02) and 55% lower amiloride-sensitive nasal transepithelial potential difference (p = 0.0003) than normoxemic patients. In profoundly hypoxemic patients, nasal epithelial messenger RNA expressions of two airway Na transporters (amiloride-sensitive epithelial Na channel and ß1- Na-K-ATPase) were not attenuated, but instead α1-Na-K-ATPase messenger RNA levels were higher (p = 0.03) than in the normoxemic patients, indicating that posttranscriptional factors may impair airway Na transport. The chest radiograph lung edema score increased after congenital cardiac surgery in profoundly hypoxemic patients (p = 0.0004) but not in patients with normoxemia or moderate hypoxemia. CONCLUSIONS: The impaired airway epithelial amiloride-sensitive Na transport activity in profoundly hypoxemic children with cyanotic congenital heart defect may hinder defense against lung edema after cardiac surgery.

Long-term outcome after treatment of pulmonary atresia with ventricular septal defect: nationwide study of 109 patients born in 1970-2007.

OBJECTIVES: Treatment of pulmonary atresia with ventricular septal defect (PA + VSD) has evolved during recent decades, but it still remains challenging. This study evaluated 41-year experience of outcome, survival and treatment of PA + VSD patients. METHODS: Patient records and angiograms of 109 patients with PA + VSD born in Finland between 1970 and 2007, and treated at the Children's Hospital, Helsinki University Central Hospital, were retrospectively analysed in this nationwide study. RESULTS: Of the 109 patients, 66 (61%) had simple PA + VSD without major aortopulmonary collateral arteries (MAPCAs). Although we observed no difference in overall survival between those with or without MAPCAs, the patients without MAPCAs had better probability to achieve repair (64 vs 28%, P < 0.0003). Only 3 patients were treated by compassionate care. Overall survival was affected by the size of true central pulmonary arteries on the first angiogram (P = 0.001) and whether repair was achieved (P < 0.0001). After successful repair, the survival rate was 93% at 1 year, 91% from the second year, and functional capacity as assessed by New York Heart Association (NYHA) I-II remained in 85% of patients alive at the end of follow-up. Palliated patients at 1, 5, 10 and 20 years of age had Kaplan-Meier estimated survival rates of 55, 42, 34 and 20%, respectively. Patients who underwent repair attempts but were left palliated with right ventricle (RV)-pulmonary artery connection and septal fenestration had better survival than the rest of the palliated patients (P = 0.001). Further, the McGoon index improved after implementation of a systemic-pulmonary artery shunt in the overall PA + VSD population (P < 0.0001). CONCLUSIONS: These findings show that achievement of repair and initial size of true central pulmonary arteries affect survival of patients with PA + VSD. Although the overall survival of patients with MAPCAs showed no difference compared with simple PA + VSD patients, they had a higher risk of remaining palliated. However, palliative surgery may have a role in treatment of PA + VSD because the size of pulmonary arteries increased after placement of systemic-pulmonary artery shunt. In addition, subtotal repair by a RV-pulmonary artery connection and septal fenestration improved survival over extracardiac palliation.

Duration of gestation and mode of delivery affect the genes of transepithelial sodium transport in pulmonary adaptation.

BACKGROUND: Respiratory distress due to inadequate lung liquid clearance is a significant problem in infants delivered late preterm or early term, especially by elective cesarean delivery (CD). Lung liquid clearance depends on epithelial ion transport and in animals is induced by glucocorticoids. OBJECTIVES: In newborn late preterm and term infants to study airway epithelial gene expressions of epithelial sodium channel (ENaC), and the serum and glucocorticoid-inducible kinase 1 (SGK1), and their association with cortisol, mode of delivery, and gestational age (GA). METHODS: Infants were delivered at 35(0/7)-41(6/7) weeks. Cortisol in umbilical cord plasma was analyzed with liquid chromatography-tandem mass spectrometry. ENaC and SGK1 mRNAs in airway epithelial cells obtained within 3 h and at 1 day postnatally were quantified with real-time PCR. RESULTS: ENaC and SGK1 mRNAs were significantly lower in late preterm and early term infants than in those ≥ 39(0/7) weeks. Significant correlations existed between both ENaC and SGK1 and cord cortisol and GA. In term infants, SGK1 mRNA at 1.5 h was higher after vaginal delivery than elective CD. CONCLUSIONS: In late preterm and early term infants, low expression of ENaC and SGK1 may parallel insufficient lung liquid clearance predisposing to respiratory distress. Lower SGK1 expression after term CD could translate into insufficient sodium and lung liquid absorption. The findings demonstrate a central role for cortisol in regulation of ENaC and potentially perinatal sodium and lung liquid clearance.

Need of transannular patch in tetralogy of Fallot surgery carries a higher risk of reoperation but has no impact on late survival: results of Fallot repair in Finland.

OBJECTIVES: Our study is a population-based evaluation of the long-term results after surgical repair for tetralogy of Fallot (TOF). All patients operated on in the country since the first procedure were identified via the Finnish research database of paediatric cardiac surgery and the Finnish population register. The follow-up was 99% completed due to comprehensive coverage of the registers. METHODS: The Finnish research database of paediatric cardiac surgery, surgical logs, diagnosis cards and computer files of the hospitals were used for data collection. The Finnish Population Register Center was used to obtain current patient status and dates of death and emigration. RESULTS: A total of 600 patients underwent surgical repair of TOF before the age of 15 years during the 46-year period from 1962 to 2007. The mean follow-up time was 23 ± 12.1 years; 513 (85%) patients were alive and living in Finland, 82 (14%) had died and 5 patients were lost to the follow-up (0.8%). A total of 40 patients (7%) died early (≤30 days) and 42 (7%) died late (>30 days) after the surgical correction. During the last two decades the early mortality rate was 1.5% and no early deaths were observed after the year 2000. A transannular patch (TAP) was used in the reconstruction of the right ventricular outflow tract in 191 (32%) of these patients and had no influence on late mortality but the event-free survival was significantly inferior in these patients. If a primary palliation was performed before the correction, the late survival was significantly inferior when compared with patients without initial palliation. Also reoperation was more common in patients with primary palliation. CONCLUSIONS: The long-term prognosis of surgically corrected TOF patients is good and has improved with each decade since the beginning of TOF surgery in Finland. Primary repair of tetralogy of Fallot predicts a lower mortality rate and longer freedom from reoperation when compared with two-stage repair. Need of a TAP in TOF surgery carries a higher risk of reoperation but has no impact on late survival.

Screening for congenital heart defects by transabdominal ultrasound - role of early gestational screening and importance of operator training.

The majority of congenital heart defects occur without identifiable risk factors. Detection rates are therefore highly dependent on the experience and expertise of the obstetrical screening operator. In the first trimester, the risk of congenital heart defects increases with increasing nuchal thickness (≥2.5 mm detects 44% of major congenital heart defects), but because of the number of false positives, the positive predictive value is only a few percent. The anatomy of major congenital heart defects may be delineated in less than half of the fetuses during early second trimester. The reported yield of congenital heart defects detection during the mid-gestational routine obstetrical screening has improved over time and detection rates up to 85% of major congenital heart defects have been reported when outflow tract and three-vessel views are included in conjunction with the four-chamber view. Improved detection rates have been achieved following screening operator training interventions combined with a low referral threshold to obtain a detailed fetal echocardiographic study.

Expression of airway epithelial sodium channel in the preterm infant is related to respiratory distress syndrome but unaffected by repeat antenatal beta-methasone.

BACKGROUND: The airway epithelial sodium channel (ENaC) is rate limiting for postnatal alveolar fluid clearance. Increased lung water content is a feature of respiratory distress syndrome (RDS), which is reduced by antenatal corticosteroid treatment in preterm infants. OBJECTIVES: Since corticosteroids also induce ENaC gene expression, we studied whether a repeat dose of antenatal beta-methasone affects postnatal expression of airway ENaC. METHODS: 17 pregnant women with imminent preterm birth were randomized to receive a single repeat dose of beta-methasone (12 mg) or placebo (repeat beta-methasone: 8 infants, gestational age (GA) 30.8 +/- 2.2 weeks; placebo: 14 infants, GA 30.4 +/- 2.7 weeks). Expression of alpha-, beta- and gammaENaC subunits in nasal epithelium 1-5 and 20-29 h postnatally was analyzed with reverse transcription-PCR. RESULTS: There were no differences between the study groups in RDS incidence or ENaC subunit expression (all p > 0.38). Regression coefficients for association of alphaENaC expression at 1-5 h with GA in infants with and without RDS differed significantly (p = 0.023). At 20-29 h, alphaENaC expression was lower in infants with RDS (p = 0.048). CONCLUSIONS: A single repeat dose of antenatal beta-methasone did not increase ENaC expression, which may in part explain the absence of reduction in RDS incidence.

G protein-coupled receptor for asthma susceptibility associates with respiratory distress syndrome.

BACKGROUND: Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) have some common features with asthma. AIM: To study whether G protein-coupled receptor for asthma susceptibility (GPRA) contributes to RDS or BPD. METHODS: A haplotype association study was performed in a case-control setting of 521 Finnish infants (including 176 preterm neonates with RDS and 37 with BPD). Immunoreactivity of GPRA isoforms A and B was determined in pulmonary samples of fetuses, term infants and preterm infants with RDS or BPD. GPRA mRNA expression was determined by quantitative real-time polymerase chain reaction (PCR) in samples from nasal respiratory epithelium of adults, term infants and preterm infants. RESULTS: In infants with RDS born at 32-35 weeks of gestation, GPRA haplotype H1 was significantly underrepresented in RDS, whereas haplotype H4/H5 was associated with an increased risk. As in asthma, GPRA B isoform was induced in bronchial smooth muscle cells in RDS and BPD. In nasal respiratory epithelium, relative GPRA mRNA expression was strong in adults, weak in preterm and slightly higher in term samples. CONCLUSIONS: The results suggest that near-term RDS and asthma share the same susceptibility and protective GPRA haplotypes. Altered GPRA expression may play a role in the pathogenesis of RDS and BPD in preterm infants.